Mesenchymal stem cells are pluripotent blast or embryonic-like cells located in blood, bone marrow, dermis and periosteum. In general, these cells are capable of renewing themselves over extended periods of time as well as, under various environmental conditions, differentiating into cartilage, bone and other connective tissue. Recently, various investigators have researched the potential for using these cells to repair or regenerate target tissues, e.g., bone, cartilage, etc. In this manner MSCs have been reported to have regenerative capabilities in a number of animal models. See Acosta et al. (2005) Neurosurg Focus 19(3):E4; Barry (2003) Novartis Found Symp. 249:86-102, 170-4, 239-41; Brisby et al. (2004) Orthop Clin. North Am. 35(1):85-89; Buckwalter and Mankin (1998) Instr Course Lect. 47:487-504; Caplan (1991) J Orthop Res. 9(5):641-650.
Recently, Centeno et al. (U.S. patent application Ser. No. 11/773,774) described a method for expanding MSC's using a growth channel and autologous platelet lysate. Also described were methods for transplanting certain levels of growth factors (platelet lysate or platelets) with the expanded MSC's to the area in a patient in need of repair. The levels of these growth factors were based on a percentage of platelet lysate needed to optimally expand the cells ex-vivo.
MSC's can readily differentiate in culture depending on cytokine exposure, environmental conditions (pressure, attachment opportunities, passage treatment, etc. . . . ), or other chemical exposure. For example, exposure to varying levels of TGF-beta, FGF, and/or PDGF can all have impacts on the final cell phenotype produced in culture. In addition, leaving cells in culture longer also has impacts on differentiation potential. Cells can be cultured for a certain visual morphology, confluence, or density, all of which has an impact on the final cell product produced and its potential for certain types of tissue repair.
In replacing or repairing tissue with MSC's, one concern is the use of autologous or non-autologous cells. While MSC's have been traditionally considered immune privileged, recent investigations have demonstrated their activation of the natural killer cell system in a foreign host. (Spaggiari, Capobianco et al. 2006) This makes the use of non-autologous cells difficult, as it is anticipated that the host's immune system will attack these foreign cells and potentially decimate the population of transplanted MSCs, thus severely limiting their repair capabilities.
There is a need in the art for MSC expansion techniques that do not use drugs or growth factors which are not FDA approved and can be effectively used to replace tissue in a patient in need thereof. This is especially true where the tissue in the patient in need of repair is cartilage. Cartilage repair is a major issue in health care which will only continue to increase as the median age in the United States continues to increase.
There is a need for autologous techniques to yield MSC and non-MSC based cartilage repair techniques.
The present invention is directed toward overcoming one or more of the problems discussed above.